loperamide itself is a p-glycoprotein inhibitor. its part of its MOA. p-glycoproteins regulate substances across the BBB

the way loperamide is structured , when it reaches its absorption , it goes into the BBB and quickly back out as fast as it went in. so it doesn't have Central Nervous System effects. only Peripheral Nervous System effects (ie GI track. why it works for diarreah, but no psychoactive high because of the lack of CNS penetration)

so people will take 100s and 100s of these 2mg pills at once bevause they "think" that's what it takes to feel anything,

but really , they're just overdosing on loperamide for the half life to kick in , approx. 5-10 hrs later, then as its recirculating in the blood at half the initial dose (mind u, they take upto 200 - 400 2mg pills) which is still alot, will now have the advantage of its initial effects (inhibiting the p-glycoprotein enzymes) and potentially allow loperamide to pass the BBB and reach the brain to cause An opioid High..

that's how they feel it if they feel anything. but they don't know that , if only they knew that THERES OTHER P-GLYCOPROTEIN INHIBITORS, that you can preload beforehand and then take a dose akin to hydromorphone (6mg-12mg ) and reach said high without the serious side effects of OVERDOSING your PNS (aka YOUR HEART) .

now, which p-glycoprotein inhibitors work best? that's up to you to discover my friend